The primary objective has been to develop sensitive and highly specific analytical techniques for the determination of psychosedative agents and their immediate metabolites in biologic fluids and to establish a therapeutic range in serum for the compounds in the treatment of patients with mental health problems. Specific efforts are currently being directed to developing analytical techniques for the analysis of doxepin (Sinequan R), amitriptyline (Elavil R), imipramine (Forfrani 1R), fluphenazine (Siqualon R), chloropromazine (Throazine R) and haloperidol (Haldo 1R). The techniques being developed utilize the electron-capture and nitrogen specific detectors of the gas-liquid cromatography to privide sufficient sensitivity to determine the pharmacologic agents at concentrations less than 1 ng/ml in microliter amounts of serum. In addition highly reliable and chemically related internal standards for the chromatography of the compounds are being evaluated to insure a low coefficient of variation in the analytical methods. Relative retention indices are also being tabulated for a large number of psychosedative and tranquilizer drugs that can be assayed at nanogram concentrations by electron-capture and nitrogen-phosphorus specific detectors. The latter data will assist laboratories in identifying unknown psychosedative compounds in accidental and intentional overdose situations. The new procedures employ simple and direct derivatizing reagents that are adaptable to any clinical or research laboratory.